CAS 5608-24-2 PRIMA-1 - Analytical Products / Alfa Chemistry

CAT	AP5608242
CAS	5608-24-2
Structure
MDL Number	MFCD04974196
Molecular Weight	185.22
InChI Key	RFBVBRVVOPAAFS-UHFFFAOYSA-N

Description	≥98% (HPLC), solid
Solubility	H2O: >10 mg/mL
Assay	≥98% (HPLC)
Color	white to off-white
Form	solid
Size	5MG, 25MG
Storage Conditions	2-8°C

p53 Reactivation With Induction of Massive apoptosis-1 (PRIMA-1) Inhibits Amyloid Aggregation of Mutant p53 in Cancer Cells

Luciana P Rangel, Giulia D S Ferretti, Caroline L Costa, Sarah M M V Andrade, Renato S Carvalho, Danielly C F Costa, Jerson L Silva

J Biol Chem. 2019 Mar 8;294(10):3670-3682.

PMID: 30602570

Prima-1 and APR-246 in Cancer Therapy

Pavlína Zatloukalová, Michaela Galoczová, Bořivoj Vojtěšek

Klin Onkol. Winter 2018;31(Suppl 2):71-76.

PMID: 31023027

PRIMA-1 and PRIMA-1 Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies

Anne Perdrix, Ahmad Najem, Sven Saussez, Ahmad Awada, Fabrice Journe, Ghanem Ghanem, Mohammad Krayem

Cancers (Basel). 2017 Dec 16;9(12):172.

PMID: 29258181

PRIMA-1 MET induces mitochondrial apoptosis through activation of caspase-2

J Shen, H Vakifahmetoglu, H Stridh, B Zhivotovsky, K G Wiman

Oncogene. 2017 Jun 22;36(25):3650.

PMID: 28192401

PRIMA-1 MET-induced neuroblastoma cell death is modulated by p53 and mycn through glutathione level

Vid Mlakar, Simona Jurkovic Mlakar, Laurence Lesne, Denis Marino, Komal S Rathi, John M Maris, Marc Ansari, Fabienne Gumy-Pause

J Exp Clin Cancer Res. 2019 Feb 12;38(1):69.

PMID: 30755224

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Case Study

PRIMA-1 Used for the Restoration of Mutant TP53 Function and Induction of Apoptosis in Esophageal Squamous Cell Carcinoma

Furukawa, Haruna, et al. Cancer science 109.2 (2018): 412-421.

PRIMA-1 (p53 reactivation and induction of massive apoptosis) is a small-molecule compound used for restoring the transcriptional activity of mutant TP53, a gene frequently mutated in esophageal squamous cell carcinoma (ESCC), with reported mutation rates exceeding 90%. This study investigated the selective antitumor effects and underlying mechanism of PRIMA-1 in ESCC cells bearing distinct TP53 genotypes.
Cell viability and apoptosis assays revealed that PRIMA-1 significantly inhibited proliferation and induced apoptosis in ESCC cell lines harboring TP53 missense mutations, but showed minimal effect in wild-type, nonsense, or frameshift TP53 backgrounds. Mechanistically, PRIMA-1 treatment led to the upregulation of the pro-apoptotic protein Noxa, a known downstream effector of TP53. Western blotting confirmed increased Noxa expression specifically in TP53 missense mutant cells. Notably, RNA interference-mediated knockdown of Noxa abolished PRIMA-1-induced apoptosis, confirming its central role in the apoptotic response.
In vivo validation using an ESCC xenograft model further demonstrated that PRIMA-1 administration significantly suppressed tumor growth and elevated Noxa levels in TP53 missense mutant tumors, whereas control treatments showed no comparable effect.
This study highlights PRIMA-1 as a promising therapeutic agent for targeting TP53 missense mutations in ESCC by inducing Noxa-mediated apoptosis, offering a precision medicine approach for patients with this aggressive cancer subtype.

PRIMA-1 Used for the Covalent Modification of Mutant p53 to Restore Tumor Suppressor Function and Induce Apoptosis

Lambert, Jeremy MR, et al. Cancer cell 15.5 (2009): 376-388.

PRIMA-1 (p53 reactivation and induction of massive apoptosis) is used for the covalent modification of mutant p53, facilitating the restoration of its wild-type function and the induction of tumor cell death. While the antitumor potential of PRIMA-1 has been extensively observed, its precise molecular mechanism involves the chemical conversion into reactive compounds capable of forming adducts with thiol groups in mutant p53 proteins.
In this study, recombinant mutant p53 proteins (His175 and Gln248) were treated with prewarmed PRIMA-1, dialyzed to remove unbound reagent, and delivered into p53-null Saos-2 osteosarcoma cells using a protein transfection system. Only PRIMA-1-treated mutant p53-unlike untreated or non-prewarmed PRIMA-1-treated samples-was able to induce marked apoptosis, as evidenced by increased sub-G1 DNA content and upregulation of the apoptosis-associated protein 14-3-3. Importantly, PRIMA-1-treated bovine serum albumin (BSA) was non-toxic, underscoring the specificity of p53 targeting.
Furthermore, antioxidant pretreatment with N-acetylcysteine failed to rescue cells from apoptosis, confirming that PRIMA-1's covalent modification of mutant p53, rather than free PRIMA-1, mediates the cytotoxic effects. These findings highlight PRIMA-1's unique mechanism: reactivating mutant p53 through thiol alkylation, triggering cell cycle arrest at G2/M and promoting apoptosis, with significant implications for designing next-generation p53-targeting therapies.

PRIMA-1 Used for the Restoration of Mutant p53 Function and Induction of Apoptosis in Breast Cancer Cells

Wang, Tao, et al. Biochemical and biophysical research communications 352.1 (2007): 203-212.

PRIMA-1 (p53 reactivation and induction of massive apoptosis) is a low molecular weight compound used to pharmacologically restore the tumor suppressor function of mutant p53-a frequent genetic alteration in over 40% of breast cancers associated with chemoresistance. This study investigates the apoptotic mechanisms triggered by PRIMA-1 in human breast cancer cells harboring p53 mutations, including MDA-231 and GI-101A, in comparison with wild-type p53 MCF-7 cells.
PRIMA-1 selectively induced apoptosis in p53-mutant cells, correlating with elevated nuclear p53 levels and enhanced phosphorylation at the Ser-15 site. Chromatin immunoprecipitation (ChIP) assays demonstrated that PRIMA-1 reestablished the DNA-binding ability of mutant p53 to pro-apoptotic gene promoters, specifically Bax and PUMA, while suppressing its interaction with the MAP4K4 promoter. Silencing of p53 using siRNA prior to PRIMA-1 exposure led to reduced expression of Bax and PUMA, confirming their dependency on restored p53 activity.
Interestingly, PRIMA-1 or the JNK inhibitor SP600125 suppressed adriamycin-induced JNK activation, indicating that PRIMA-1-induced apoptosis occurs via a JNK-independent pathway.
These results underscore the potential of PRIMA-1 as a targeted therapeutic agent to reactivate p53-dependent apoptotic pathways in breast cancers with mutant p53, offering a promising approach to overcome chemoresistance.